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Fallout: New Vegas shares a similar set of skills to its predecessor Fallout 3, but some small changes have been made. For example, small guns and big guns are now all included in one skill 'Guns'.The following section covers the skills, perks and traits that are featured in the game.

The game places the player in the role of a courier working for the Mojave Express, known simply as "the Courier". While delivering a package known only as "the Platinum Chip" to New Vegas, the Courier is ambushed by Benny (voiced by Matthew Perry), leader of one of the casinos in New Vegas, who steals the package, shoots the player in the head, and leaves the body in a shallow grave. A robot named Victor witnesses the shooting and brings the courier to Doctor Mitchell in Goodsprings.At this point, the player enters into character creation and defines the Courier's skills, attributes, name, gender, age and appearance. Although traumatized, the player begins their journey, following Benny to avenge the attack and recover the stolen package, all while exploring the Mojave Wasteland.

Fallout: New Vegas introduces factions into the mix, and each group has strengths and weakness. A level of trust has to be gained from the faction groups, in order to gain perks and benefits of an alliance. Trust from the factions are usually accomplished in Quests. Alliance with one factions typically does come at cost of another rival faction.